Articles in 2018

A small-molecule manganese-based catalyst has been developed for the selective oxidation of strong methylene C–H bonds in the presence of more oxidatively labile aromatic functionality. This reaction enables the late-stage oxidative derivatization of medicinally relevant compound scaffolds and may also prove useful for diversifying aromatic drugs and natural products, as well as helping to quickly identify their metabolites.

The concept of ‘interrupted transfer hydrogenation’ is presented, allowing the reductive hydroxymethylation of pyridinium and quinolinium salts at the C3 position. Mechanistic studies show the reaction occurs through an initial reversible iridium hydride reduction, followed by trapping of an enamine generated in situ before a final irreversible iridium-hydride reduction.

Intersystem crossing (ISC) is a radiationless process that is important in many photophysical systems. It has now been observed to take place in the exit channel for the reaction of ground-state atomic oxygen with alkylamines.

Preparation of well-defined N-glycans is very demanding, which hampers progress in glycoscience. Now, a biomimetic synthetic approach has been developed in which a readily available bi-antennary glycan can be converted in ten or fewer steps into multi-antennary N-glycans. This approach enables each arm to be uniquely extended by glycosyltransferases to give complex branched N-glycans.

Rapamycin and FK506 are macrocycles that contain an FKBP-binding domain and an effector domain responsible for interacting with their respective targets, mTOR and calcineurin. Now, a 45,000-compound macrocycle library has been synthesized by fusing oligopeptides with synthetic FKBP-binding domains. Screening and subsequent optimization yielded a highly potent FKBP-dependent inhibitor of hENT1.

Widely used palladium-mediated cross-couplings typically operate via a handful of fundamental reaction steps. Now, the reactivity between palladium and C–C σ-bonds has been described. This carbopalladation enables the coupling of organoboronic esters and aryl triflates across a C–C σ-bond of a bicyclo[1.1.0]butane to form disastereomerically pure trisubstituted cyclobutanes.

In native photosystem II (PSII), multi-chromophore antennas surround the reaction centre, capturing light and triggering the quantized (four-flashes) photo-oxidation of water to oxygen. The PSII ‘quantasome’ is the most efficient photo-electrolyser built so far. An artificial quantasome has now been developed; it is specifically designed for oxygen evolution by self-assembling light-harvesting-perylene bisimides with a ruthenium polyoxometalate water-oxidation catalyst.

The creation of a viable technology that enables precise control over the monomer sequence in synthetic polymers remains a significant challenge. High-purity sequence-defined polyethers with readily tailored side-chain functionalities have now been made through liquid-phase iterative synthesis combined with size-exclusion molecular sieving and real-time monitoring.

Some porous coordination polymers (PCPs) are known to be flexible and guest-responsive. Now, the guest-induced sharp, reversible structural transformation of the surface of a single-crystalline PCP has been visualized by in situ liquid-phase atomic force microscopy. This local response occurred at a guest concentration that was too low to trigger changes to the bulk crystal.

The S_N2 reaction, a fundamental process associated with ionic chemistry, can be incorporated into a photochemical approach to creating radicals from alkyl electrophiles. This method occurs readily under visible-light irradiation, exhibits broad functional-group tolerance, and enables the formation of open-shell intermediates from substrates that are incompatible with traditional radical-generating strategies.

Synthetic gene circuits encapsulated in lipid membrane compartments are often employed as artificial cell mimics, but these lack the complex behaviour of biological tissues. Now, spatial information based on chemical gradients has been used to engineer non-trivial dynamics such as signal propagation and differentiation in an artificial multicellular system.

Heteromultivalency, which involves the simultaneous interactions of more than one type of ligand with more than one type of receptor, is common in biological systems but challenging to engineer artificially. Now, a heteromultivalent platform prepared by co-assembling cyclodextrin and calixarene amphiphiles has shown self-adaptive peptide binding with high affinity. The platform was used to sequester amyloid β-peptides, reducing amyloid cytotoxicity.

Solid acid heterogeneous catalysts are widely used in industrial chemical processes, but understanding the exact molecular structures responsible for catalytic activity has proved difficult. Now, the structure of the strong Brønsted acid site for a sulfated zirconium-based metal–organic framework has been shown to consist of a specific arrangement of adsorbed water and sulfate moieties on the zirconium clusters.

Typical methods for the enantioselective α-functionalizations of ketones join ketone enolate nucleophiles with carbon or heteroatom electrophiles. We report an umpolung strategy to achieve this transformation with masked ketone electrophiles and a wide range of conventional heteroatom and carbon nucleophiles catalysed by a metallacyclic iridium catalyst in high yield and enantioselectivity.

The use of Li or Na as electrodes in Li-Na alloy–O₂ batteries creates formidable challenges for both safety and stability because of their oxidative corrosion and the growth of dendrites and cracks on their surface. Now, an aprotic bimetal Li-Na alloy–O₂ battery with high cycling stability has been developed using a Li-Na eutectic alloy anode and an electrolyte additive.

Nitrogen fixation—the direct conversion of dinitrogen into ammonia or other nitrogen-containing products—is notoriously difficult to promote under mild conditions. Now, the reactivity of a multimetallic diuranium(iii) complex recently found capable of reducing and functionalizing N₂ has been explored, replacing its nitride bridge with an oxo bridge, which resulted in a markedly different reactivity.

Synthetic receptors can be used to help understand biological systems, but rarely compete in terms of affinity or selectivity. Now, a glucose-binding compound has been prepared that, despite its symmetry and simplicity, can match all but the strongest glucose-binding proteins. The high binding affinity and outstanding selectivity of this receptor may translate into biomedical applications.

N-heterocyclic carbenes (NHCs) are valuable surface anchors, but their use has remained limited to either spherical or planar nanomaterials. Now, they have been grafted onto gold nanorods through a bidentate ligand featuring a thiolate and a NHC–gold complex. The resulting nanorods are robust towards a wide range of harsh conditions and show promise for photothermal therapy.

The preparation of conjugates between proteins and small molecules is often challenging and requires several synthetic steps to functionalize each component for conjugation. Now, a conjugation methodology that leverages an electrophilic Se–S bond of selenocysteine to create bioconjugates between polypeptides and complex small molecules has been described.

A 27 kDa photosensitizer protein (PSP) has now been developed and used to design a miniature photocatalytic CO₂-reducing enzyme. Visible light drives the PSP efficiently to the long-lived triplet excited state (PSP*), and then to a super-reducing radical (PSP^•), which is strong enough to reduce many CO₂-reducing catalysts. The 3D structure of PSP^• at 1.8 Å resolution was determined by X-ray crystallography.